Approximately 1.2 million Americans were admitted to treatment for cannabis use disorders last year. Clinical trials indicate that a majority of those who enter treatment for cannabis problems relapse, and relapse rates are comparable to those observed for other drugs of abuse. Currently, there are no accepted pharmacotherapies to aid the treatment of cannabis use disorders. Disturbed sleep is one of the most prominent symptoms of the cannabis withdrawal syndrome, and recent laboratory research has demonstrated that heavy cannabis users experience clinically significant sleep problems following abrupt cessation of use. Specifically, data from clinical surveys and prospective laboratory studies suggest that sleep disturbance during abstinence can precipitate relapse to cannabis use, and heavy cannabis users exhibit disruptions in sleep architecture and continuity during abstinence that meet benchmark criteria for a diagnosis of insomnia. Similar abstinence induced effects on sleep and sleep-related risk of relapse are known to occur during withdrawal from other drugs of abuse, and, importantly, research has shown that adding sleep improvement interventions to alcohol treatment programs can significantly improve clinical outcomes. This suggests that sleep improvement interventions could reduce relapse among cannabis users trying to quit. The proposed project aims to address two important gaps in understanding the relationship between sleep and cannabis use: 1) abstinence-induced sleep disturbance has not been assessed prospectively or objectively in cannabis users seeking treatment, thus, the external validity of retrospective surveys and laboratory studies is uncertain and 2) it is unclear if amelioration of sleep disturbance during a quit attempt will result in improved clinical outcomes (e.g. relapse prevention). The proposed study will be a double blind outpatient clinical trial in which eligible participants will receive one of two 12-week treatment interventions: 1) psychosocial therapy (MET/CBT) + 12.5 mg extended-release zolpidem, or 2) MET/CBT + placebo. Objective and subjective measures of sleep quality and architecture will be obtained throughout the study while participants attempt to quit use of cannabis in their home environment. Sleep assessments include polysomnography (intake, treatment weeks 1, 6, 10, and 12, and 3 month follow- up), actigraphy (daily) and sleep diaries (daily). Participants will complete MET/CBT therapy modules once per week, complete assessments and provide observed urine specimens for toxicological testing twice weekly, and self-administer study medication nightly during treatment. The mechanism by which we believe extended- release zolpidem will benefit study participants is an improvement in sleep. The relationship between sleep and cannabis use outcomes will be determined via planned mediation analysis. Outcomes from this study will help inform the treatment of cannabis use disorders, will extend the scientifi understanding of the interrelationship of cannabis use and sleep, and will help guide future pharmacotherapy research. PUBLIC HEALTH RELEVANCE: The number of people seeking treatment for marijuana-related problems is on the rise, yet there is no currently accepted medication proven to help them quit. Frequent marijuana users have reported that they have trouble sleeping when they try to quit, and that the loss of sleep can lead to relapse. This research is designed to measure the severity of sleep problems in people as they are trying to quit heavy use of marijuana, and to investigate the ability of an FDA approved sleep medication, extended-release zolpidem (Ambien CR(R)), to improve quit rates among people trying to stop using marijuana.